Is Long-Term Benzodiazepine Use a Risk Factor for Cognitive Decline? Results of a Systematic Review

Abstract

Background and Aims. Benzodiazepines have been widely used for long periods of time despite their adverse effects. The acute effects on cognition are well established. However, less is known about the long-term effects. This study critically reviewed existing evidence of the association between long-term exposure to benzodiazepines and risk of cognitive decline in adults. Methods. A systematic review with narrative synthesis was conducted. PubMed and PsycINFO databases were searched using combinations of keywords related to “benzodiazepines” and “cognitive function” from database inception to 12 February 2018 to identify prospective longitudinal studies. The records were evaluated for relevance according to the inclusion and exclusion criteria. Results. Fourteen studies involving 2145 long-term benzodiazepine users were included. Meta-analysis was not undertaken because the combined result would not be meaningful as the included studies differed in several key aspects such as frequency and duration of benzodiazepine use, follow-up periods, cognitive domains, cognitive tests, scoring systems, and statistical analysis. The definition of long-term benzodiazepine use was problematic in all the studies. The exposure was determined by measures which were assumed to represent the whole period in-between the follow-ups. Only 3 of the 14 studies provided support for an association between long-term benzodiazepine use and cognitive decline with a small to medium effect size. However, these three studies used different methods to assess the strength of this association. Global cognitive functioning, verbal memory, intelligence, psychomotor speed, and speed of processing were the cognitive domains affected which also varied across these three studies. Conclusions. Little evidence of an association between long-term benzodiazepine use and a higher risk of cognitive decline among the general adult population was found. However, discrepancies among the results and inconsistencies regarding the cognitive domains affected and methodological limitations prevent definite conclusions. Therefore, future research with prospective studies specially designed would be of great value.

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies

“…Consistent with previous systematic reviews, our meta-analysis suggests no impairment in global cognition among elderly BZD users ( 49 , 50 ). Interestingly, studies with young adults showed opposing results ( 51 , 52 ), suggesting BZD use significantly impairs participants’ global cognitive functioning.…”

Residual Injurious Symptoms and Its Association With Neurodegenerative Outcomes in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Retrospective, Longitudinal Follow‐up Study

“…Nonetheless, a multicenter study found that patients with RBD who converted to dementia rather than parkinsonism had a higher percentage use of clonazepam at baseline, at which the authors conjectured that more severe RBD might have led to a higher risk of dementia with a consequent requirement of more medication 35 . In the general population, there was a controversial association between benzodiazepine usage and future risk of dementia, 36‐39 and a recent large cohort study did not reveal any association between the use of benzodiazepines and subsequent dementia in patients with affective disorders 40 . In our study, there was a higher maximum dosage of clonazepam used in patients with RIS than those without.…”

“…20 Nonetheless, a multicenter study found that patients with RBD who converted to dementia rather than parkinsonism had a higher percentage use of clonazepam at baseline, at which the authors conjectured that more severe RBD might have led to a higher risk of dementia with a consequent requirement of more medication. 35 In the general population, there was a controversial association between benzodiazepine usage and future risk of dementia, [36][37][38][39] and a recent large cohort study did not…”

Patterns of Psychoactive Medication Use in Community-Dwelling Older Adults in the US in 2016: A Descriptive Cross-Sectional Study

“…Alprazolam is a short-acting benzodiazepine and is associated with temporary memory impairment and slowing of psychomotor functions in older adults (Pietrzak et al, 2012). Although there is no strong evidence of the long-term effect of alprazolam and benzodiazepine medications more broadly on global cognitive functioning, the literature suggests that efforts should be made to taper doses and remove patients from benzodiazepines as soon as possible to avoid tolerance and physical dependence (Nader & Gowing, 2020; Navy et al, 2018). One of the reasons for higher overall use of anxiolytics, sedatives, and hypnotics in low-income individuals can be associated with the available evidence that individuals with low income are more likely to have diagnosed mood disorders or anxiety than high-income individuals (Sareen et al, 2011).…”